The purpose of this work is to evaluate drug therapy in chronic pain syndromes that are considered resistant to known approaches: syndromes caused by injury to nerve, such as diabetic neuropathy and herpes zoster, and syndromes caused by advanced cancer in which tolerance to the analgesic effects of narcotics has developed. A 12-week study of patients with painful diabetic neuropathy is underway. Amitriptyline is compared to active placebo under double-blind conditions. Patients record levels of pain and mood 5 times a day. The effect of drug on perception of heat by nociceptive nerve fibers is evaluated during clinic visits. The data will be analyzed to learn if amitriptyline is effective in this condition, and if the effects on pain and mood are independent. Analysis of data from the first 11 patients show an analgesic effect; 29 of the full cohort of 30 patients have been accrued. Patients with post-herpetic neuralgia enter a similar chronic drug study, comparing amitriptyline to lorazepam to placebo, as well as a single-dose analgesic study, comparing codeine, ibuprofen, clonidine and placebo; all of these drugs may work by interacting with analgesic systems in the injured nerve or adjacent spinal cord. Twenty-five of a planned 40 patients are enrolled. In advanced cancer, conventional opiate drugs may lose their effectiveness because of the development of tolerance at the mu opiate receptor. Studies are planned using stable analogues of endogenous enkephalins, which produce analgesia by action at the delta-receptor; these agents retain effectiveness in animals made tolerant to mu-receptors. The relative potency of intrathecal DADL-enkephalin and morphine will be compared in patients with varying degrees of tolerance to morphine, and the relative potency of intramuscular metkephamid to morphine will be compared in morphine-naive and tolerant patients.